The objective of this investigation is to clearly delineate, at the cellular and molecular level, the immunogenesis of the humoral anti- erythrocyte autoantibody response - the primary pathogenetic effector of auoimmune hemolytic anemia. These studies, utilizing NZB mice, will include: 1) purification and characterization of the pathogenetic erythrocyte autoantigen; 2) characterization of interactions between the lymphoid system and autoantigen; 3) delineation of the role of the X autoantigen molecule in the initiation, regulation and genetic segregation of the anti- erythrocyte autoantibody response; 4) characterization of the B lymphocyte events and delineation of focal aberrations and critical points of control of specific B lymphocyte kinetics; and 5) delineation of the influence of regulatory mechanisms, including T lymphocytes an other "host factors", which are responsible for the initiation and regulation of B lymphocyte proliferatton and derepression intrinsic to the synthesis of pathogenetic autoantibody and the pathogenesis of autoimmune hemolytic anemia.